Distribution of the carcinogenic tryptophan pyrolysis product Trp-P-1 in control, 9-hydroxyellipticine and. beta. -naphthoflavone pretreated mice
- Uppsala Biomedical Centre (Sweden). Dept. of Pharmacology
- Kungliga Karolinska Mediko-Kirurgiska Inst., Stockholm (Sweden)
Autoradiograms obtained 1-4 h after i.v. injection of the /sup 14/C-labelled carcinogenic tryptophan pyrolysis product Trp-P-1 to albino and pigmented mice showed a pronounced uptake of radioactivity in the lymphatic system, in the endocrine system and in the liver, kidney medulla and brain. High radioactivity was present in the excretory pathways, predominantly in the bile/intestinal contents. At longer post-injection times most of the labelled substance had left the tissues, except for the liver. Trp-P-1 is known to be activated by cytochrome P-448. The uptake of radioactivity in the liver could be reduced by pretreatment with the cytochrome P-448 inhibitor 9-hydroxyellipticine suggesting that the observed accumulation of radioactivity in the liver was partly due to metabolites of Trp-P-1. After pretreatment with the cytochrome P-448 inducer ..beta..-naphthoflavone, the administration of Trp-P-1 resulted in a highly selective accumulation of radioactivity in the lung parenchyma, exceeding all other tissues. ..beta..-Naphthoflavone pretreatment also increased the uptake of radioactivity in the kidney cortex and small intestinal mucosa. As indicated by a high labelling of the pigmented tissues of the maternal and fetal eye, the carcinogen and/or its metabolites were accumulated in melanin.
- OSTI ID:
- 5014682
- Journal Information:
- Carcinogenesis (N.Y.); (United States), Vol. 4:10
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
CARCINOGENS
TISSUE DISTRIBUTION
AUTORADIOGRAPHY
CARBON 14 COMPOUNDS
IN VIVO
MICE
PYROLYSIS PRODUCTS
RESPONSE MODIFYING FACTORS
TRYPTOPHAN
AMINO ACIDS
ANIMALS
AROMATICS
AZAARENES
AZOLES
CARBOXYLIC ACIDS
DISTRIBUTION
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
INDOLES
LABELLED COMPOUNDS
MAMMALS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PYRROLES
RODENTS
VERTEBRATES
550501* - Metabolism- Tracer Techniques